Analysis of the contrasting pathogenicities induced by the D222G mutation in 1918 and 2009 pandemic influenza A virusesReport as inadecuate


Analysis of the contrasting pathogenicities induced by the D222G mutation in 1918 and 2009 pandemic influenza A viruses


Analysis of the contrasting pathogenicities induced by the D222G mutation in 1918 and 2009 pandemic influenza A viruses - Download this document for free, or read online. Document in PDF available to download.

Publication Date: 2015-03-24

Journal Title: Journal of Chemical Theory and Computation

Publisher: ACS

Volume: 11

Issue: 5

Pages: 2307-2314

Language: English

Type: Article

Metadata: Show full item record

Citation: Shang, C., Whittleston, C. S., Sutherland-Cash, K. H., & Wales, D. J. (2015). Analysis of the contrasting pathogenicities induced by the D222G mutation in 1918 and 2009 pandemic influenza A viruses. Journal of Chemical Theory and Computation, 11 (5), 2307-2314.

Description: This is the final version of the article. It first appeared from ACS via http://pubs.acs.org/doi/abs/10.1021/ct5010565.

Abstract: In 2009, the D222G mutation in the hemagglutinin (HA) glycoprotein of pandemic H1N1 influenza A virus was found to correlate with fatal and severe human infections. Previous static structural analysis suggested that, unlike the H1N1 viruses prevalent in 1918, the mutation did not compromise binding to human α2,6-linked glycan receptors, allowing it to transmit efficiently. Here we investigate the interconversion mechanism between two predicted binding modes in both 2009 and 1918 HAs, introducing a highly parallel intermediate network search scheme to construct kinetically relevant pathways efficiently. Accumulated mutations at positions 183 and 224 that alter the size of the binding pocket are identified with the fitness of the 2009 pandemic virus carrying the D222G mutation. This result suggests that the pandemic H1N1 viruses could gain binding affinity to the α2,3-linked glycan receptors in the lungs, usually associated with highly pathogenic avian influenza, without compromising viability.

Sponsorship: This work was supported by the ERC and the EPSRC.

Identifiers:

This record's URL: http://dx.doi.org/10.1021/ct5010565http://www.repository.cam.ac.uk/handle/1810/247970

Rights: Attribution 2.0 UK: England & Wales

Licence URL: http://creativecommons.org/licenses/by/2.0/uk/





Author: Shang, ChengWhittleston, Chris S.Sutherland-Cash, Kyle H.Wales, David J.

Source: https://www.repository.cam.ac.uk/handle/1810/247970



DOWNLOAD PDF




Related documents